Abstract-Synuclein is a presynaptic protein recently identified as a specific component of Lewy bodies (LB) and Lewy neurites. The aim of this study was to assess the morphology and distribution of -synuclein immunoreactivity in cases of dementia with LB (DLB), and to compare -synuclein with ubiquitin immunostaining. We examined substantia nigra, paralimbic regions (entorhinal cortex, cingulate gyrus, insula and hippocampus), and neocortex (frontal and occipital association cortices) with double -synuclein and ubiquitin immunostaining in 25 cases meeting neuropathological criteria for DLB. -Synuclein immunostaining was more specific than ubiquitin immunostaining in that it differentiated LB from globose tangles. It was also slightly more sensitive, staining 45% more intracytoplasmic structures, especially diffuse -synuclein deposits that were ubiquitin negative. In addition to LB, -synuclein staining showed filiform and globose neurites in the substantia nigra, CA23 regions of the hippocampus, and entorhinal cortex. A spectrum of -synuclein staining was seen in substantia nigra: from diffuse cloud-like inclusions to aggregated intracytoplasmic inclusions with variable ubiquitin staining to classic LB. We hypothesize that these represent different stages in LB formation.